Our studies are concerned with the interaction of pneumococci and the alternative pathway of C3-C9 activation. A number of different aspects of the interaction of pneumococci and the alternative pathway will be studied. We will study the biological significance of the alternative pathway in the host's defense against infection. We hope to identify the components of the alternative pathway that are required for pneumococcal opsonization. We hope to identify that component of the pneumococcus that initiates activation of the alternative pathway. Finally, we hope to identify the defect in alternative pathway function in Sickle Cell Disease that is reponsible for increased susceptibility to pneumococcal infection.